Cell division is a fundamental cellular process about which little is known at the molecular level. Defects in cell division may lead to cancer and other diseases. The aim of this proposal is to use a combination of molecular genetics and biophysical approaches to answer the question: How does a cell know where to divide? The model of choice for this proposal is S. pombe, a single-cell eukaryote with simple cytoskeletal architecture, powerful genetics, and amenability for live cell imaging. In S. pombe the position of the division plane appears to be dictated by the position of the nucleus. Furthermore, nuclear positioning at the cell center is microtubule dependent. This proposal aims to use biophysical (e.g., UV ablation, high-resolution multi-mode digital microscopy, laser cutting, etc ...) and molecular genetic (e.g., gene knockout, mutant phenotype analysis, GFP-tagging, etc ...) approaches to: I) determine how the nucleus and/or the microtubules may produce forces that position the nucleus; (II) determine the function of a novel S. pombe gene, rsp1, that participates in microtubule organization and nuclear positioning.